IMP4

Summary

IMP4 (IMP U3 small nucleolar ribonucleoprotein 4, HGNC:30856) is a protein-coding gene on chromosome 2q21.1, encoding U3 small nucleolar ribonucleoprotein protein IMP4 (Q96G21). Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

The protein encoded by this gene, along with IMP3 and MPP10, is part of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP) complex. This complex is necessary for the early cleavage steps of pre-18S ribosomal RNA processing. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 92856 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 72 total
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_033416

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30856
Approved symbol	IMP4
Name	IMP U3 small nucleolar ribonucleoprotein 4
Location	2q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC19606, BXDC4
Ensembl gene	ENSG00000136718
Ensembl biotype	protein_coding
OMIM	612981
Entrez	92856

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 12 protein_coding, 11 retained_intron, 1 nonsense_mediated_decay

ENST00000259239, ENST00000409649, ENST00000409935, ENST00000428740, ENST00000452955, ENST00000456713, ENST00000460100, ENST00000460766, ENST00000462357, ENST00000462392, ENST00000464432, ENST00000470672, ENST00000473689, ENST00000475074, ENST00000477375, ENST00000490895, ENST00000495606, ENST00000859438, ENST00000859439, ENST00000859440, ENST00000859441, ENST00000927812, ENST00000951188, ENST00000951189

RefSeq mRNA: 16 — MANE Select: NM_033416 NM_001320304, NM_001320305, NM_001320306, NM_001320307, NM_001320309, NM_001320310, NM_001320311, NM_001371725, NM_001371726, NM_001371728, NM_001371730, NM_001371731, NM_001371732, NM_001371733, NM_001371734, NM_033416

CCDS: CCDS2160

Canonical transcript exons

ENST00000259239 — 9 exons

Exon	Start	End
ENSE00001070705	130346356	130347967
ENSE00001813756	130342897	130342935
ENSE00003520818	130343086	130343194
ENSE00003529709	130345567	130345699
ENSE00003553218	130346201	130346274
ENSE00003635872	130346018	130346112
ENSE00003640369	130345779	130345933
ENSE00003657765	130344629	130344712
ENSE00003692975	130345376	130345485

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.5899 / max 274.1558, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22501	50.5899	1825

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.28	gold quality
gastrocnemius	UBERON:0001388	96.42	gold quality
muscle of leg	UBERON:0001383	95.97	gold quality
body of stomach	UBERON:0001161	95.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.49	gold quality
lower esophagus	UBERON:0013473	95.48	gold quality
right lobe of liver	UBERON:0001114	95.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.39	gold quality
mucosa of transverse colon	UBERON:0004991	95.36	gold quality
left coronary artery	UBERON:0001626	95.31	gold quality
prefrontal cortex	UBERON:0000451	95.19	gold quality
granulocyte	CL:0000094	95.18	gold quality
apex of heart	UBERON:0002098	95.16	gold quality
triceps brachii	UBERON:0001509	95.15	gold quality
heart left ventricle	UBERON:0002084	95.13	gold quality
coronary artery	UBERON:0001621	94.99	gold quality
cardiac ventricle	UBERON:0002082	94.95	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.95	gold quality
right coronary artery	UBERON:0001625	94.91	gold quality
muscle organ	UBERON:0001630	94.91	gold quality
skeletal muscle organ	UBERON:0014892	94.91	gold quality
right atrium auricular region	UBERON:0006631	94.86	gold quality
popliteal artery	UBERON:0002250	94.70	gold quality
tibial artery	UBERON:0007610	94.69	gold quality
left adrenal gland	UBERON:0001234	94.66	gold quality
omental fat pad	UBERON:0010414	94.66	gold quality
peritoneum	UBERON:0002358	94.64	gold quality
left adrenal gland cortex	UBERON:0035825	94.64	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.56	gold quality
right adrenal gland	UBERON:0001233	94.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	721.53
E-MTAB-7249	no	223.68
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting IMP4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-4801	98.96	69.42	2096

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 1)

• DDX10 promotes human lung carcinoma proliferation by U3 small nucleolar ribonucleoprotein IMP4. (PMID:33973712)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	imp4	ENSDARG00000054540
mus_musculus	Imp4	ENSMUSG00000026127
rattus_norvegicus	Imp4	ENSRNOG00000013285
drosophila_melanogaster	CG11920	FBGN0039274
caenorhabditis_elegans		WBGENE00014083

Paralogs (1): RPF1 (ENSG00000117133)

Protein

Protein identifiers

U3 small nucleolar ribonucleoprotein protein IMP4 — Q96G21 (reviewed: Q96G21)

Alternative names: Brix domain-containing protein 4

All UniProt accessions (6): B8ZZ47, B9A008, Q96G21, E7ENR5, F8WCN0, H0Y714

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Component of a heterotrimeric complex containing IMP3, IMP4 and MPHOSPH10. Interacts with MPHOSPH10.

Subcellular location. Nucleus. Nucleolus.

RefSeq proteins (16): NP_001307233, NP_001307234, NP_001307235, NP_001307236, NP_001307238, NP_001307239, NP_001307240, NP_001358654, NP_001358655, NP_001358657, NP_001358659, NP_001358660, NP_001358661, NP_001358662, NP_001358663, NP_219484* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007109	Brix	Domain
IPR044281	IMP4/RPF1	Family

Pfam: PF04427

UniProt features (2 total): chain 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96G21-F1	89.47	0.57

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72312	rRNA processing
R-HSA-8868773	rRNA processing in the nucleus and cytosol
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 151 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_RIBOSOME_BIOGENESIS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_MATURATION_OF_SSU_RRNA, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, TAANNYSGCG_UNKNOWN, REACTOME_METABOLISM_OF_RNA, GOCC_90S_PRERIBOSOME, GOCC_PRERIBOSOME, GOCC_SMALL_SUBUNIT_PROCESSOME, GOCC_NUCLEOLUS, BLALOCK_ALZHEIMERS_DISEASE_DN

GO Biological Process (4): rRNA processing (GO:0006364), maturation of SSU-rRNA (GO:0030490), ribosomal small subunit biogenesis (GO:0042274), ribosome biogenesis (GO:0042254)

GO Molecular Function (4): snoRNA binding (GO:0030515), rRNA primary transcript binding (GO:0042134), protein binding (GO:0005515), rRNA binding (GO:0019843)

GO Cellular Component (8): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), nucleolus (GO:0005730), preribosome (GO:0030684), small-subunit processome (GO:0032040), Mpp10 complex (GO:0034457), nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleolus	3
ribosome biogenesis	2
ribonucleoprotein complex biogenesis	2
RNA binding	2
cellular anatomical structure	2
nuclear lumen	2
nuclear protein-containing complex	2
RNA processing	1
rRNA metabolic process	1
rRNA processing	1
ribosomal small subunit biogenesis	1
rRNA binding	1
binding	1
intracellular membraneless organelle	1
ribonucleoprotein complex	1
preribosome	1
t-UTP complex	1
90S preribosome	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1998 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IMP4	MRPL2	Q5T653	576
IMP4	MRPS12	O15235	544
IMP4	MRPL17	Q9NRX2	480
IMP4	DDX28	Q9NUL7	447
IMP4	MRPL11	Q9Y3B7	446
IMP4	CSDC2	Q9Y534	400
IMP4	ORC1	Q13415	393
IMP4	MXRA8	Q9BRK3	365
IMP4	ACAT2	Q9BWD1	357
IMP4	RPF2	Q9H7B2	353
IMP4	GNL2	Q13823	352
IMP4	IMP3	Q9NV31	352
IMP4	ZFPL1	O95159	351
IMP4	BRIX1	Q8TDN6	351
IMP4	NIP7	Q9Y221	350

IntAct

121 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ZBTB7B	IMP4	psi-mi:“MI:0915”(physical association)	0.670
IMP4	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.670
IMP3	MPHOSPH10	psi-mi:“MI:0914”(association)	0.670
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
ZBTB7B	IMP4	psi-mi:“MI:0915”(physical association)	0.560
IMP4	MPHOSPH10	psi-mi:“MI:0915”(physical association)	0.560
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
KRR1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
	IMP4	psi-mi:“MI:0915”(physical association)	0.400
IMP4	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (139): IMP4 (Two-hybrid), IMP4 (Affinity Capture-MS), IMP4 (Co-fractionation), IMP4 (Co-fractionation), IMP4 (Co-fractionation), NAT10 (Co-fractionation), NOL10 (Co-fractionation), IMP4 (Reconstituted Complex), IMP4 (Affinity Capture-MS), IMP4 (Two-hybrid), IMP4 (Two-hybrid), IMP4 (Affinity Capture-MS), IMP4 (Affinity Capture-MS), IMP4 (Affinity Capture-MS), IMP4 (Affinity Capture-MS)

ESM2 similar proteins: G0S488, G0S616, G0SF80, O13823, O14180, O14206, O62518, P12531, P30190, P34524, P36160, P38789, P38805, P53941, P54073, Q01879, Q08235, Q09817, Q0VD01, Q12153, Q196X4, Q54DJ0, Q54JN0, Q54N44, Q5PQR5, Q5R631, Q5R947, Q5RJS9, Q6BYD9, Q6C804, Q6FNN7, Q6IQU6, Q755T8, Q7S302, Q7TND5, Q8AVP1, Q8VHZ7, Q96G21, Q96X45, Q9ASU7

Diamond homologs: O13823, O14180, O62518, P53941, P54073, Q0VD01, Q5PQR5, Q5R631, Q5R947, Q5RJS9, Q6BYD9, Q6C804, Q6FNN7, Q6IQU6, Q755T8, Q7TND5, Q8AVP1, Q8VHZ7, Q96G21, Q9H9Y2, Q9VKB4, Q9YC08, P38805, Q975H1, Q5JDM5, O26776, O74104, Q467K0, Q58012, Q6M0M3, Q8TQ11, Q8TZI2, Q9UXB9, Q9V200

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MPHOSPH10	“up-regulates activity”	IMP4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peptide chain elongation	19	35.5×	2e-23
Viral mRNA Translation	19	35.5×	2e-23
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	19	35.1×	2e-23
Selenocysteine synthesis	19	33.6×	4e-23
Eukaryotic Translation Termination	19	33.6×	4e-23
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	19	32.9×	4e-23
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	19	32.9×	4e-23
Formation of a pool of free 40S subunits	19	31.3×	1e-22

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	21	39.7×	8e-26
ribosomal large subunit biogenesis	7	31.7×	2e-07
rRNA processing	17	24.6×	3e-17
ribosomal small subunit biogenesis	10	23.2×	2e-09
translation	20	21.0×	7e-19
regulation of alternative mRNA splicing, via spliceosome	6	14.9×	2e-04
negative regulation of translation	6	12.0×	7e-04
RNA processing	5	11.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

72 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1866 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:130345793:A:C	S152R	0.998
2:130345795:C:A	S152R	0.998
2:130345795:C:G	S152R	0.998
2:130345796:C:G	H153D	0.998
2:130345818:C:A	A160D	0.998
2:130346103:T:A	I227K	0.998
2:130345459:A:C	S94R	0.997
2:130345461:T:A	S94R	0.997
2:130345461:T:G	S94R	0.997
2:130345644:C:G	C128W	0.997
2:130345809:G:A	G157D	0.997
2:130345643:G:A	C128Y	0.996
2:130345667:T:C	L136P	0.996
2:130345791:T:A	V151D	0.996
2:130346103:T:G	I227R	0.996
2:130346112:G:C	R230P	0.996
2:130345402:T:C	Y75H	0.995
2:130345469:T:A	L97H	0.995
2:130345642:T:C	C128R	0.995
2:130345808:G:C	G157R	0.995
2:130345890:C:A	P184H	0.995
2:130345926:G:A	G196D	0.995
2:130346253:G:A	G248R	0.995
2:130346253:G:C	G248R	0.995
2:130346254:G:A	G248E	0.995
2:130346365:T:A	I258N	0.995
2:130345478:T:C	F100S	0.994
2:130345567:G:A	E103K	0.994
2:130345571:T:C	L104P	0.994
2:130345605:C:A	N115K	0.994

dbSNP variants (sampled 300 via entrez): RS1000095126 (2:130341416 C>T), RS1000327396 (2:130344162 A>T), RS1000490505 (2:130342695 A>C,G), RS1001074332 (2:130347813 C>T), RS1001333652 (2:130347597 C>A), RS1001713789 (2:130345496 G>T), RS1001756408 (2:130345041 C>G), RS1002322825 (2:130341306 G>C), RS1003066533 (2:130342516 G>T), RS1003265265 (2:130343879 G>T), RS1003386114 (2:130344150 A>G), RS1003677034 (2:130341995 T>A,C), RS1003938501 (2:130344485 C>A,T), RS1004940446 (2:130345807 T>C), RS1005205304 (2:130343522 G>A)

Disease associations

OMIM: gene MIM:612981 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	5
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
bisphenol A	affects expression	1
beta-lapachone	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Coumestrol	increases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	decreases expression	1
Ribonucleotides	affects binding	1
Silicon Dioxide	increases expression	1
T-2 Toxin	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.